Neoplastic Transformation of Rat Colon Epithelial Cells by Expression of Activated Human K‐ras

Somatic mutations of the K‐ras oncogene play an important role in colorectal carcinogenesis. We determined whether rat colon epithelial cells could be transformed by introducing retroviruses carrying the activated human K‐ras oncogene alone. Primary epithelial cells from the rat distal colon were in...

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Bibliographic Details
Published in:Cancer science 1998-06, Vol.89 (6), p.615-625
Main Authors: Sugiyama, Kenji, Otori, Kazuhiko, Esumi, Hiroyasu
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carcinogenesis
Cell culture
Cell Division
Cell lines
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Cell Transformation, Neoplastic
Cells, Cultured
Colon
Colon - metabolism
Colon - pathology
Colon - virology
Colonic Neoplasms - genetics
Epithelial cell
Epithelial cells
Epithelial Cells - metabolism
Epithelial Cells - pathology
Female
Fundamental and applied biological sciences. Psychology
Genes, ras
Human K‐ras
Humans
Keratins - metabolism
key words
Mice
Mice, Nude
Molecular and cellular biology
Neoplasm Transplantation
ras Proteins - analysis
Rat
Rats
Rats, Inbred F344
Retroviridae - genetics
RNA, Messenger - analysis
Rodents
Transfection
Transformation
Transformed cells
Tumors
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Summary:Somatic mutations of the K‐ras oncogene play an important role in colorectal carcinogenesis. We determined whether rat colon epithelial cells could be transformed by introducing retroviruses carrying the activated human K‐ras oncogene alone. Primary epithelial cells from the rat distal colon were infected with retroviruses carrying wild‐type and two types of activated K‐ras (asp and val at codon 12) cDNAs. Cells infected with the wild‐type K‐ras virus showed no change in morphology and died within 3 weeks, whereas the activated K‐ras virus‐infected cells underwent morphological changes within 3 days and continued to proliferate. From these cells, several cell lines were subsequently established. Epithelial cells transformed by activated K‐ras formed colonies in soft agar culture and tumors in athymic nude mice. Multiple copies of human K‐ras genes and large amounts of K‐ras mRNAs and proteins were found in the transformed cells. These data suggest that overexpression of activated K‐ras transforms rat colon epithelial cells.
ISSN:0910-5050
1347-9032
1349-7006
1876-4673
DOI:10.1111/j.1349-7006.1998.tb03263.x